Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I
| Autor: | Wenwu Zhang, Marnie L. Gruen, Kelly A. Posey, MacRae F. Linton, Alyssa H. Hasty, Michelle R. Plummer, Sergio Fazio |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD36 Antigens
Apolipoprotein E medicine.medical_specialty Apolipoprotein B Lipoproteins Gene Expression QD415-436 Biochemistry Mice chemistry.chemical_compound Endocrinology High-density lipoprotein scavenger receptor class B type I Internal medicine polycyclic compounds medicine small dense low density lipoproteins Animals Obesity RNA Messenger Particle Size Receptors Immunologic Scavenger receptor Crosses Genetic remodeling Mice Knockout Receptors Scavenger Leptin receptor Apolipoprotein A-I biology Cholesterol nutritional and metabolic diseases Lipase Cell Biology Scavenger Receptors Class B hepatic lipase Lipoproteins LDL Mice Inbred C57BL Liver chemistry biology.protein lipids (amino acids peptides and proteins) Hepatic lipase Lipoproteins HDL Lipoprotein |
| Zdroj: | Journal of Lipid Research, Vol 46, Iss 9, Pp 2007-2014 (2005) |
| ISSN: | 0022-2275 |
| DOI: | 10.1194/jlr.m500181-jlr200 |
| Popis: | Obese mice without leptin (ob/ob) or the leptin receptor (db/db) have increased plasma HDL levels and accumulate a unique lipoprotein referred to as LDL/HDL1. To determine the role of apolipoprotein A-I (apoA-I) in the formation and accumulation of LDL/HDL1, both ob/ob and db/db mice were crossed onto an apoA-I-deficient (apoA-I(-/-)) background. Even though the obese apoA-I(-/-) mice had an expected dramatic decrease in HDL levels, the LDL/HDL1 particle persisted. The cholesterol in this lipoprotein range was associated with both alpha- and beta-migrating particles, confirming the presence of small LDLs and large HDLs. Moreover, in the obese apoA-I(-/-) mice, LDL particles were smaller and HDLs were more negatively charged and enriched in apoE compared with controls. This LDL/HDL1 particle was rapidly remodeled to the size of normal HDL after injection into C57BL/6 mice, but it was not catabolized in obese apoA-I(-/-) mice even though plasma hepatic lipase (HL) activity was increased significantly. The finding of decreased hepatic scavenger receptor class B type I (SR-BI) protein levels may explain the persistence of LDL/HDL1 in obese apoA-I(-/-) mice. Our studies suggest that the maturation and removal of large HDLs depends on the integrity of a functional axis of apoA-I, HL, and SR-BI. Moreover, the presence of large HDLs without apoA-I provides evidence for an apoA-I-independent pathway of cholesterol efflux, possibly sustained by apoE. |
| Databáze: | OpenAIRE |
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